期刊
EMBO REPORTS
卷 21, 期 2, 页码 -出版社
WILEY
DOI: 10.15252/embr.201948097
关键词
anxiety; cholinergic neurons; medial habenula; social interaction; TMEM16A
资金
- Bio-Synergy Research Project [NRF-2017M3A9C4092979]
- National Research Foundation in Korea [NRF-2016M3C7A1904149, NRF-2017M3C7A1079694]
- National Research Council of Science AMP
- Technology of the Korean government [CRC-15-04-KIST]
- KBRI basic research program through Korea Brain Research Institute - Ministry of Science and ICT [19-BR-03-02]
- National Research Council of Science & Technology (NST), Republic of Korea [CRC-15-04-KIST] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2016M3C7A1904149] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
TMEM16A, a Ca2+-activated Cl- channel, is known to modulate the excitability of various types of cells; however, its function in central neurons is largely unknown. Here, we show the specific expression of TMEM16A in the medial habenula (mHb) via RNAscope in situ hybridization, immunohistochemistry, and electrophysiology. When TMEM16A is ablated in the mHb cholinergic neurons (TMEM16A cKO mice), the slope of after-hyperpolarization of spontaneous action potentials decreases and the firing frequency is reduced. Reduced mHb activity also decreases the activity of the interpeduncular nucleus (IPN). Moreover, TMEM16A cKO mice display anxiogenic behaviors and deficits in social interaction without despair-like phenotypes or cognitive dysfunctions. Finally, chemogenetic inhibition of mHb cholinergic neurons using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) approach reveals similar behavioral phenotypes to those of TMEM16A cKO mice. We conclude that TMEM16A plays a key role in anxiety-related behaviors regulated by mHb cholinergic neurons and could be a potential therapeutic target against anxiety-related disorders.
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